Our objective is to determine if systemic and pulmonary vascular control and reactivity are altered during early, experimental diabetes mellitus in pigs. The increased incidence of micro- and macrovascular diseases in diabetics is probably the result, in part, of early, subtle changes in vascular metabolism and biochemistry. Although many years might be required before such changes lead to morphologic lesions, it is possible that early, potentially important alterations would be reflected in abnormal vascular function. Since the pulmonary circulation is apparently spared from diabetic angiopathies, a comparative study of the effects of diabetes on systemic and pulmonary vascular reactivity would be especially informative. We will study control and alloxan-diabetic pigs at 2 and 12 months after treatment. Cardiovascular responses to direct, humoral stimulation with angiotensin II, norepinephrine, and prostaglandin F2 alpha and to neural reflex stimulation elicited by body tilting will be studied in intact, anesthetized animals. Pulmonary vascular reactivity and cardiovascular reflexes will also be examined during alveolar hypoxia. To provide a more direct evaluation of vascular reactivity, further studies involving the contractile responses of isolated systemic and pulmonary arteries to potassium chloride, norepinephrine, angiotensin II and prostaglandin F2 alpha at normal and elevated glucose levels will be performed. These experiments will indicate whether early diabetes results in abnormal vascular function and at what level of the vascular control system the abnormality occurs.